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Albumin is a main biomarker of denutrition severity. Since 2019, the French National Authority of Health (HAS) recommends an immunologic technique as a reference for measuring albuminemia. In a context of partial recovery by the laboratory of GHBS (using colorimetric method with bromcresol purple) of the biological activity of the dialysis center, until then carried out by the Ouest biology - Biolor laboratory (using colorimetric method with bromcresol green) and in order to standardize practices in the healthcare sector, we compared 3 albumin assay techniques: immunoturbidimetric (Diagam®), BCG (Siemens®), BCP (Siemens®) on Siemens Atellica PLCs. The albumin level of 183 patient samples was measured. We show an overestimation of the dosage by the BCG (+ 5.46 g/L compared to IT) and an interference related to the inflammatory state of the patient during the dosage with this technique, as well as an underestimation of the dosage by the BCP (- 0.91 g/L relative to the IT), increased in patients with renal injury. This biological difference is added to a discrepancy in clinical conclusions. A change in dosing technique from BCG to BCP may impact the biological follow-up of patients and the PMSI score (mean difference of - 6.67 g/L between BCG and BCP while the classification of the severity of denutrition uses thresholds set in steps of 5 g/L). This variability of results should be taken into account by the clinicians and constitutes an argument in favor of the standardization of laboratories around a reference technique.

This article aims to place the phosphatidylethanol (PEth) blood test in the detection area of ethanol consumption causing alcohol-related disorders, to present the current methods of analysis, data on interpretation, some practical applications and the prospects of use of this biomarker. PEth is a minor metabolite of ethanol. Among nearly 50 PEth counterparts, PEth 16:0/18:1 is the most abundant. The interest that PEth brings compared to other biomarkers is the extended window of detection of ethanol consumptions. Indeed, it has a blood elimination half-life of approximately 5 days, which offers estimated alcohol consumption for a 21 to 28 days period. Thus, the detection of alcohol use disorders and withdrawal monitoring (systematically combined with urinary ethylglucuronide) in addictology and in liver pre- and post-transplantation are today its main routine applications. Nevertheless, additional data are still necessary to improve the interpretation of measured concentrations and to reach a consensus on interpretation cut-offs of blood PEth concentrations.

International audience; Les anti-PD-1 s’imposent dernièrement comme un traitement de référence dans de nombreux cancers métastatiques. Ils présentent l’avantage d’une efficacité significative doublée d’un profil de toxicité favorable en monothérapie. Les taux et durées de réponse sont toutefois très variables, ce qui implique, vu leur coût, d’identifier des biomarqueurs prédictifs de réponse. Dans cette revue de la littérature, nous nous intéressons aux biomarqueurs de réponse des immunothérapies anti-PD1 et anti-CTLA-4. L’expression de PD-L1 par les cellules tumorales et du micro-environnement évaluée par immunohistochimie est prédictive de réponse pour certains cancers mais reste une approche mal standardisée avec différents anticorps, différents seuils de positivité et différentes cibles (tumeur ou micro-environnement). Il s’agit aussi d’une expression dynamique au cours du temps et hétérogène donc souvent discordante entre biopsies et pièces opératoires. Les lymphocytes circulants pourraient représenter un biomarqueur prédictif notamment via la mesure du ratio polynucléaires neutrophiles sur lymphocytes (NLR), ratio simple à réaliser en pratique courante. Un taux de néoantigènes élevé serait également associé à une réponse plus importante ce qui expliquerait les taux de réponses particulièrement élevés des tumeurs avec instabilité micro-satellitaire. Des signatures génomiques pourraient également prédire la sensibilité aux anti-PD1. Par ailleurs, la présence de certaines bactéries de la flore intestinale favoriserait la réponse immunitaire antitumorale même si le mécanisme demeure mal compris. Enfin, des signatures d’expression de cytokines, médiatrices de la réponse immune, pourraient constituer des biomarqueurs pertinents. Plusieurs biomarqueurs de réponse potentiels semblent donc intéressants mais aucun n’est encore prospectivement validé à ce jour.

To date, Thyroid-Associated Orbitopathy (TAO), an autoimmune inflammatory disease affecting the eye, remains poorly characterised and its diagnosis challenging. The aim of this study was to investigate the tears of the TAO patients in order to identify potential biomarkers. Two independent quantitative Tandem Mass Tag™ 6-plex experiments were done. After in-solution digestion and isoelectric fractionation, the 12 fractions were analysed with a LTQ Orbitrap Velos coupled to a liquid chromatography. Raw files were searched against Swiss-Prot-AC database using Proteome Discoverer software, with a false discovery rate of 1% at peptide and protein levels. The differential proteins were then verified using orthogonal approaches in independent patients. Globally, 712 tear proteins were quantified with 2 unique peptides. Interestingly, cystatin c (TAO/controls ratio: 1.53), alpha-1 antichymotrypsin (ratio: 1.70) and retinal dehydrogenase (ratio: 0.68), displaying differential levels in the tears of TAO patients using proteomics experiments emerged as highly promising biomarkers after verification. In conclusion, this proteomics study supports the idea that tears reflect biological modifications occurring in a disease context and can therefore be a promising fluid for biomarker discovery. Moreover, our study identified three candidates that could in the future open new avenues in the diagnosis of TAO disease. Significance Thyroid associated orbitopathy (TAO) is the most common disease affecting the orbit. Moreover, the later, severe stages of the disease can be sight threating [1] . On the other hand, the early sign and symptoms can be mistaken with other ocular pathologies [2] . Here we explore the modification of the tear content of the TAO patients using proteomics strategies and we proposed three new biomarker candidates, which could allow the early diagnosis of the disease and prompt action to prevent more severe stages. Moreover, our findings could also help to better understand the pathophysiology of the disease.

Iron deficiency, due to blood loss or malabsorption, is commonly observed in geriatric practice. In elderly people, association of inflammatory diseases to iron loss makes diagnosis of absolute iron deficiency sometimes difficult. In case of inflammation, the interpretation of usual biomarkers of iron deficiency (serum ferritin, transferrin saturation, serum iron) may be difficult. The recent discovery of the role of hepcidine in the iron homeostasis, in physiological and pathological situation, contributes to better understanding of the iron regulation. The aim of this short paper is to underline some specificities of elderly iron physiology, to explain hepcidine's role in physiological and pathological situations and to propose a diagnostic approach for a better interpretation of usual biomarkers, in order to differentiate absolute iron deficiency and functional iron deficiency.

Sclerostin is an osteocyte-specific glycoprotein secreted by the osteocyte and involved in the regulation of bone mass. High sclerostin levels are associated with osteoporosis, whereas low sclerostin levels are correlated with higher bone mineral density. It seems interesting to investigate a potential association between sclerostin levels and vascular calcifications since sclerostin is considered as a potent inhibitor of bone formation. In chronic kidney disease, serum sclerostin levels rise as renal function declines. Preliminary studies show a positive association between serum sclerostin and vascular calcification, but the link between sclerostin and survival of patients remains unclear in the absence of large-scale studies.

Complex interactions existing between cardiac and renal diseases led to define 5 types of so-called cardiorenal syndromes. This classification is based on the organ primarily involved and the acute or chronic failure. The mutual impact of renal and cardiac functions makes it difficult to evaluate and manage patients with cardiorenal syndromes and worsen morbidity and mortality. This review seeks to discuss the place of biomarkers in diagnosis, management and follow-up of patients with cardiorenal syndromes. Biomarkers can be classified as functional (creatinine, cystatin C…) or lesional (neutrophil gelatinase-associated lipocalin, urinary cystatin C…) renal markers and functional (natriuretic peptides…) or lesional (troponin, fatty acid binding protein) cardiac markers. A last kind of biomarkers reflects the dialogue between heart and kidney (renin-angiotensin-aldosteron-system, indicators of activation of arginine vasopressin system) or the systemic impact (inflammation, oxidative stress…). In order to evaluate accurately the complex interactions that are the basis of cardiorenal syndromes, a multi-marker approach seems nowadays necessary.

Although numerous diagnostic and/or prognostic biomarkers are proposed in the literature, only a limited number of them are finally used in daily practice. The necessary steps to prove their clinical interest include: 1) an exhaustive clinical and statistical evaluation demonstrating not only the added value of the marker with regard to the existing validated tools but also the modification of the clinical practice induced by the knowledge of the result of the biomarker; 2) an evaluation of the pre-analytical, and analytical performances of its measure necessary to the reliability of the results; 3) an evaluation of its biological variation. These steps are a major prerequisite to an effective, reliable and optimal clinical interpretation of the biomarker, and should be validated for each routine biomarker.

International audience; Circulating citrulline is emerging as an innovating biomarker candidate for assessment of intestinal function. Amino acid synthesized by enterocytes of intestinal mucosal, citrulline is not included in proteins or nutrition products and is a precursor for production of arginine by the kidney. Plasma citrulline is, in clinical situation, an established biomarker of enterocyte functional metabolic mass (trophicity) in children and in adult patients due to its high relation to active functional small bowel remnant length in intestinal diseases (short bowel, extensive enteropathies, intestinal toxicity of chemotherapy and radiotherapy. Plasma citrulline concentration (30-50 μmol/L), independent of nutritional status, if less than 10 μmol/L can give an objective threshold for nutrition parenteral use in case of intestinal failure due to enterocyte abnormalities or lack. Its regular dosage allows the monitoring of intestinal function except in case of significant renal failure.

Discordances were observed with thyroid reference range from BCF Access 2 analyser. The purpose of this study was to establish specific reference range value for free thyroxine (FT4), free triiodothyronine (FT3) and thyrotropin (TSH) in adult Meaux Hospital population. Samples from 308 adults aged from 18 to 65 years were studied. Patients (no pregnancy and no iodine contrast media used) after informed consent, were exempted of thyroidal, cardiac, renal, multiple-organ-failure illnesses. Thyroid assays, anti-TPO and anti-TG levels were measured on the BCF Access2 immunoassay system. This work exposes difficulties to define range values in order to better use the biomarker in the clinical context.

As the failure of several recent Phase III drug development programmes bears witness, the clinical development of “disease-modifying” drugs in Alzheimer’s disease has been confronted with challenging methodological difficulties. Taking into account the financial stakes involved taking drug candidates to the Phase III stage of development, and the risk of investing time and resources fruitlessly in the evaluation of poor candidate drugs, the crucial decision remains whether to proceed from Phase II to Phase III (Go/Nogo). The aim of Phase II studies is to select a molecule likely to be effective in Phase III, but also to eliminate candidate-drugs with an inadequate effect. No consensus currently exists on the best possible design of Phase II studies to inform the Go/Nogo decision optimally. The challenges in choosing the best study design relate to the target population, the end-point criteria used, in particular the use of biomarkers, the experimental protocol, and the study duration. The objective of the Round Table (RT) was to gather the opinions of French experts from the academic, industrial, and regulatory world in order to arrive at a consensus recommendation for the best possible design to be used in Phase II studies in Alzheimer’s disease.

The roundtable 1 “Relevance of the evaluation criteria used in clinical trials for Alzheimer’s disease” made reference to the guideline published by the EMEA (European Medicines Agency) in July 2008 on the development of new treatments for Alzheimer’s disease (AD) and other dementias, and addressed principally two of the three indications listed in the guideline: symptomatic improvement and disease-modification (primary prevention was hardly discussed). The discussions focussed on two main aspects: improvement of the selection of patients in clinical trials and clinical evaluation and biomarkers. The following suggestions were made: – Reinforce the interest for clinical trials at the early stages of AD (including prodromal stage), particularly for disease-modifiers. – Strengthen the research centers’ expertise with biomarkers, in a perspective of subsequent use in clinical trials, either for the description of the patients included, or as part of selection criteria. Furthermore, ongoing intercenter validation studies, in France, of neuro-imaging and biomarker assays in CSF, are essential for preparing multicenter clinical trials. – Facilitate the conduct of ancillary studies with biomarkers, grafted on clinical studies. – Further develop the training and experience of raters with functional scales, which are now required as one of the two primary endpoints in pivotal clinical trials, and with the additional items of ADAS-cog (Alzheimer’s Disease Assessment scale, Cognitive sub scale), which are useful for the early stages of AD. – Improve knowledge of functional clinical scales by in depth analysis of available databases, through public/private collaborations. – Improve knowledge of relationship between rating scales used in clinical trials and tools used in clinical practice (which are usually different), in order to provide supporting evidence for the interpretation of the clinical relevance of clinical trials results. – Consider the potential needs of adaptation of rating scales to the societal changes, in particular for the evaluation of cognitive performance. – Discuss the possibility of measures for extending data protection for candidate disease-modifiers, considering the negative impact for all players of the constraints of duration and the difficulties of clinical trials. – Further discuss the ethics and acceptability of placebo-controlled monotherapy studies on durations of 6-9 months.